PARTICIPATION OF THE ENDOCANNABINOID SYSTEM IN THE REGULATION OF PLACENTAL NITRIC OXIDE IN RAT .

M FARINA, M CELLA, M SORDELLI, M CERVINI, S BILLI AND A M FRANCHI.

Los Cocos, Córdoba, Argentina

Simposio; III Simposio Latinoamericano de Interacción Materno Fetal y Placenta: de la Investigación a la Clínica (III SLIMP).; 2007

Normal fetal growth and development is dependent on sufficient transport of nutrients, ions and water across the placenta. The nitric oxide (NO) produced by NO synthase (NOS) is important to maintain a suitable blood flow and inhibit the immune response. Recent works demonstrate that the endogenous cannabinoid, anandamide (AEA), exerts dual effects on NO levels. It has been demonstrated that high circulating levels of AEA results from low expression of its metabolizing enzyme fatty acid amide hydrolase (FAAH). We hypothesized that AEA may have important local actions on the development of the placenta. The aim of the present work was to determine the participation of the endocannabinoid system on NOS activity in the rat placenta. Here, we show that CB1 and CB2 receptors were detected on placental tissues from day 13 to day 22 of gestation by western blot. NOS activity diminished on day 18 until the end of pregnancy. On the other hand, the activity and protein expression of FAAH increased (p<0.001) during the same period, suggesting that AEA levels may be crucial in the physiology of placenta. Interestingly, NOS activity was diminished when the rat placenta (d18) was incubated in the presence of AEA (10-9M) or URB (inhibitor of FAAH). This effect was reverted only when the tissues were co-incubated with antagonists of CB1 (AM 251) and CB2 (AM 630) receptors. We demonstrated that prostaglandins were not involved in the inhibition of the NOS activity since the incubation of tissues with AEA + Indometacine, a nonselective inhibitor of cyclooxigenases, did not modify NOS activity. These findings suggest that the placenta may form a barrier preventing maternal-fetal transfer of anandamide and/or modulates local levels of anandamide by regulation of FAAH expression with gestation.